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Objective To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with gabapentin for treatment of recurrent pain after trigeminal radiofrequency thermocoagulation.Methods Forty patients of both sexes suffering from recurrent pain after trigeminal radiofrequency thermocoagulation,who refused surgical treatment,aged 45-80 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,with visual analog scale score ≥4,with the course of recurrent pain 0.5-17.0 months,were randomized into 2 groups (n =20 each) using a random number table:gabapentin group (group A) and gabapentin plus rTMS group (group B).The patients were treated with 2 courses of rTMS in total (5 days for 1 course,1 time per day) and with the second course at a 2-day interval in group B.Effective analgesia and pain relief were recorded within 6 months after treatment,and the therapeutic efficacy was evaluated according to the modified Macnab criteria.The daily consumption of gabapentin and development of rTMS-and gabapentin-related adverse reactions were recorded.Results No rTMS-related adverse reactions were found in group B.Compared with group A,the rates of effective analgesia and pain relief were significantly increased,the therapeutic efficacy was enhanced,the daily consumption of gabapentin was decreased,and the incidence of gabapentin-related adverse reactions was decreased in group B (P＜0.05).Conclusion Combination of rTMS and gabapentin produces better efficacy than gabapentin alone when used to treat the recurrent pain after trigeminal radiofrequency thermocoagulation,and the safety is good.
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Objective To evaluate the effect of gabapentin on Cav3.2 channels in the dorsal root ganglia ( DRG) of rats with neuropathic pain. Methods Thirty male Sprague?Dawley rats, aged 6-7 weeks, weighing 225-275 g, were divided into 3 groups ( n=10 each) using a random number table:sham operation group ( S group) , neuropathic pain group ( NP group) and gabapentin group ( G group) . In NP and G groups, neuropathic pain was induced by chronic constriction injury to the left sciatic nerve. Starting from 7th day after operation, gabapentin 100 mg∕kg in 1 ml of normal saline was injected intraper?itoneally twice a day for 7 consecutive days in group G, and the equal volume of normal saline was given twice a day for 7 consecutive days in S and NP groups. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured on day 3 before operation and on postoperative days 3, 7 and 14. After the last measurement of pain thresholds on the postoperative day 14, 4 rats were sacrificed for determination of Cav3. 2 mRNA expression ( by real?time polymerase chain reaction) and Cav3.2 protein expression (by Western blot) in the DRG. Results Compared with S group, the MWT was significantly decreased, and TWL was significantly shortened on postoperative days 3, 7 and 14, and the expression of Cav3.2 protein and mRNA in the DRG was significantly up?regulated in group NP, and the MWT was significantly decreased, and TWL was significantly shortened on postoperative days 3 and 7 ( P0.05) . Compared with NP group, the MWT was significantly increased, and TWL was signif?icantly prolonged on the postoperative day 14, and the expression of Cav3.2 protein and mRNA in the DRG was significantly down?regulated in group G ( P<0.05) . Conclusion The mechanism by which gabapentin attenuates neuropathic pain may be related to inhibition of the function of Cav3.2 channels in the DRG of rats.
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Objective To evaluate the effect of gabapentin for treatment of neuropathic pain induced by bilateral sciatic nerve chronic constriction injury (bCCI) of rats.Methods Forty-eight female SPF Sprague-Dawley rats,weighing 180-200 g,aged 7-9 weeks,were randomly divided into 4 groups (n =12 each) using a random number table:control group (C group),sham operation group (S group),bCCI group,and bCCI + gabapentin group (G group).Gabapentin 100 mg/kg was intraperitoneally injected once at 15 min before operation and twice a day during 7-13 days after operation for 7 consecutive days.The bilateral mechanical paw withdrawal threshold (MWT),thermal paw withdrawal latency (TWL) and number of cold-stimulated paw withdrawal were measured before operation (baseline) and at 1,3,6,8,10,14 days after operation.Results Compared with C group,the bilateral MWT was significantly decreased,and the bilateral TWL was shortened in bCCI and G groups,and no significant change was found in MWT and TWL in S group.Compared with bCCI group,the bilateral MWT was significantly increased,the bilateral TWL was prolonged,and no significant change was found in the number of cold-stimulated paw withdrawal in G group.Conclusion Gabapentin can relieve thermal and mechanical hyperalgesia induced by bCCI,however,it exerts no effect on cold allodynia in rats.
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Objective To evaluate the efficacy of gabapentin for prevention of post-thoracotomy pain syndrome (PTPS).Methods Sixty-nine ASA physical status Ⅰ or Ⅱ patients of both sexes,aged 46-69 yr,weighing 47-78 kg,scheduled for elective resection for lung cancer under general anesthesia combined with epidural block,were randomly divided into 2 groups using a random number table:group A (n =36) and group B (n =33).In group A,gabapentin 300 mg was given orally at 2 h before operation and gabapentin 100 mg was given orally three times a day from 1st day after operation until 10th day after operation.Group B received placebo instead of gabapentin.Epidural blockade with ropivacaine and sufentanil was performed before induction of anesthesia and the level of block was controlled at T4-10.Patient-controlled epidural analgesia (PCEA) was performed within 3 days after operation and VAS scores were maintained ≤ 3.The development of pain (numeric rating scale score ＞ 4) within 6 months after operation and the duration were recorded.The consumption of propofol and remifentanil during operation and the number of attempts for PCEA after operation were recorded.The adverse reactions such as postoperative drowsiness,dizziness,fatigue were also recorded.Results Compared with B group,the incidence of pain within 6 months after operation was significantly decreased,the duration of pain was shortened (P ＜ 0.05),and no significant changes were found in the consumption of propofol and remifentanil during operation and the number of attempts for PCEA after operation in A group (P ＞ 0.05).No adverse reactions developed in group B.Mild dizziness and fatigue occurred in 2 patients in group A.Conclusion Gabapentin (continuous application at 2 h before operation and 10 days after operation) can reduce the development of PTPS in patients with no obvious adverse reactions.
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Objective To investigate the effects of gabapentin on high-voltage-activated calcium currents in dorsal root ganglion (DRG) neurons in mice with oxaliplatin-induced neuropathic pain (NP). Methods Pathogen-free male Kunming mice aged 6 weeks weighing 20-25 g were used in this study. NP was induced by injection of intraperitoneal oxaliplatin 3 mg/kg. Successful induction of NP was defined as the mechanical paw withdrawal threshold (MWT) measured at 3 d after oxaliplatin administration decreased to 40% of the baseline ( before administration of oxaliplatin). Forty-one mice in which NP was successfully induced were randomly divided into 2 groups: NP group ( n = 20) and gabapentin group (group G, n = 21 ). Another 10 normal mice served as control group (group C). At 3 days after oxaliplatin administration, gabapentin 100 mg/kg was injected intraperitoneally once a day for 3 consecutive days in group G, while C and NP groups received the equal volume of normal saline.MWT to von Fray filament stimulation was measured immediately before and 1-3 days after gabapentin administration (T1-4). After the last measurement of MWT, bilateral L4.5 DRG was collected and neurons were isolated. The high-voltage-activated calcium currents were recorded using whole-cell patch-clamp technique. The peak current density and the voltage where half of the current was activated ( Va1/2 ) or inactivated ( Vi 1/2 ) were calculated. Results Compared with group C, MWT at T1-4 was decreased, the peak current density and Vi1/2 were significantly increased in group NP, and MWT at T1 was decreased in group G ( P ＜ 0.05). There was no significant difference in the peak current density, Vi1/2 and Va1/2 between C and G groups ( P ＞ 0.05). MWT at T2-4 was significantly increased, while the peak current density and Vi1/2 were significantly decreased in group G compared with group NP (P ＜ 0.05). Conclusion Gabapentin can reduce oxaliplatin-induced NP in mice through inhibiting high-voltage-activated calcium currents and promoting the inactivation of the channels in DRG neurons.
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Objective To investigate the effect of gabapentin on high voltage active calcium currents in the injured dorsal root ganglion (DRG) neurons in a rat model of neuropathic pain.Methods Pathogen-free male SD rats aged 4-6 weeks were used in this study. The animals were anesthetized with intraperitoneal pentobarbital soclium 50 mg/kg. L_5 spinal nerve was ligated between DRG and sciatic nerve and cut distal to the ligature. The animals were decapitated on the 14th postoperative day. L_5 DRG was isolated and the neurons in the ganglion were enzymatically dissociated. The high voltage active calcium current was recorded using whole-cell patch-clamp technique.Results Gabapentin inhibited the peak calcium current in the injured DEG neurons. Peak calcium current was decreased by gabapentin 100 μmol/L and both activation and steady-state inactivation curve shifted to more hyperpolarized potentials. Conclusion Gabapentin can inhibit high voltage active in the injured DRG neurons in a rat model of neuropathic pain. The alteration in the inactivation of the electrophysiological properties may be involved in the mechanism.
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Objective To investigate the effects of different doses of gabapentin on streptozotocin (STZ)-induced diabetic neuropathic pain in rats.Methods Male SD rats aged 6 weeks weighing 180-200 g were used in this study. Diabetes ntellitus ( DM) was induced by intraperitoneal STZ 60 mg/kg and confirmed one week later by blood glucose =16.7 mmol/L before breakfast. The DM rats were randomly divided into 4 groups ( n = 6 each) : gabapentin groups received intraperitoneal gabapentin 30, 60 and 120 mg/kg twice a day (at 9:00 am and 3:00 pm) for 3 weeks respectively and control group received intraperitoneal normal saline 0.6 ml instead of gabapentin. The paw withdrawal threshold to von Frey filament stimulation was measured before and at 30, 60, 120, 180, 240 min after first gabapentin injection and once a week for 3 weeks. Results After gabapentin 60 and 120 mg/kg, the paw withdrawal threshold to mechanical stimuli was significantly increased and lasted for about 4 h. The analgesic effect peaked at 60 min after IP gabapentin injection. Normal saline and gabapentin 30 mg/kg had no significant analgesic effect. The degree of analgesia was significantly decreased at day 14 and 21 of treatment with gabapentin 60 and 120 mg/kg as compared with that at 60 min after gabapentin injection. Conclusion The hyperalgesia and allodynia in rats with diabetes mellitus can be effectively reversed by gabapentin 60 and 120 mg/kg,while long-term use of gabapentin can induce drug tolerance.
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Objective To investigate the effect of gabapentin on the activation of glial cells in the spinal cord after chronic constrictive injury (CCI) to sciatic nerve in rats.Methods Twenty-four male SD rats weighing 180-220 g were randomly divided into 3 groups (n = 8 each): group Ⅰ sham operation (group S), group Ⅱ CCI and group Ⅲ gabapentin + CCI. Right sciatic nerve was exposed and 4 loose ligatures were placed with 6-0chromic catgut. Seven days after operation gabapentin 50 mg/kg in 5 ml was given by intragastric gavage twice a day for 5 days in group Ⅲ. Paw withdrawal threshold to mechanical stimulation with von Frey filaments was measured one day before (baseline) and at 7, 15 d after operation. The animals were killed at 15 d after operation. The lumbar segment L4-5 of the spinal cord was removed. Immunohistochemical double mark technique was used to detect the activation of astrocytes and microglias in the spinal cord. Results Paw withdrawal threshold to mechanical stimulation was significantly decreased on the 7th and 15th day after CCI operation in group CCI as compared with group S. After 5 day treatment with gabapentin, the withdrawal threshold to von Frey hair stimulation was significantly higher in group Ⅲ than in group Ⅱ . The activation of astrocytes and microglias in the spinal cord was significantly enhanced in group CCI as compared with group S. Treatment with gabapentin significantly inhibited CCI-induced activation of astrocytes and microglias in the spinal cord. ConclusionGabapentin reduces neuropathic pain by inhibiting activation of glial cells in the spinal cord.
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Objective To investigate the effects of intrathecal (IT) gabapentin on the analgesic efficacy of morphine in a rat model of incisional pain. Methods Forty-eight male SD rats in which IT catheters were successly inserted according to the method described by Yaksh were randomly divided into 6 groups ( n = 8 each): Ⅰ sham operation group, Ⅱ incisional pain group, Ⅲ GBP 50 μg group, Ⅳ morphine 2.5 μg group, Ⅴ morphine 5 μg group, and Ⅵ morphine 2.5 μg + gabapentin 50 μg group. In group Ⅰ , IT artificial cerebrospinal fluid (ACSF)10 μl was injected and then 1.4% isoflurane was inhaled for 5 min. IT ACSF 10 μl, gabapentin 50μg and morphine 2.5 and 5 μg were injected 30 min before the establishement of the model in group Ⅱ -Ⅴ respectively. Paw withdrawl threshold (PWT) to mechanical stimulation and paw withdrawal latency (PWL) to a thermal nociceptive stimulus were measured at 2 h after the establishement of the model. Results Compared with group Ⅰ , MWT was significantly decreased and TWL was significantly shortened in group Ⅱ , Ⅲ and Ⅳ ( P ＜ 0.05), but no significant change in MWT and TWL was found in group Ⅴ and Ⅵ (P＞0.05). Compared with group Ⅱ , MWT was significantly increased and TWL was significantly prolonged in group Ⅴ and Ⅵ (P ＜ 0.05), but no significant change in MWT and TWL was found in group Ⅲ and Ⅳ/ ( P ＞ 0.05). MWT was significantly decreased and TWL was significantly shortened in group Ⅲ and Ⅳ compared with group Ⅵ ( P ＜ 0.05). Conclusion IT gabapentin enhances the analgesic efficacy of morphine in a rat model of incisional pain.